Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019829 (Hodgkin's disease)
 30,247 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A computer model of a neocortical pyramidal cell has been constructed using ideas similar to those used for hippocampal pyramidal cells. This model has been applied to the study of (a) repetitive firing, and (b) the paroxysmal depolarizing shift (PDS), an important intracellular event during seizures. Although calcium spikes have not been demonstrated directly in neocortical cells, we have postulated (by analogy with hippocampal pyramidal cells) a dendritic calcium conductance and a 'slow potassium' conductance modulated by intracellular calcium ion. With these dendritic ionic conductances, the model is able to reproduce the following experimental features of neocortical pyramidal cells: the afterdepolarization and succeeding afterhyperpolarization after an antidromic spike, and the f-I (firing rate-injected current) curve. Some of the differences between 'fast' and 'slow' pyramidal tract neurons (PTNs) -- narrower spikes and a steeper f-I curve in the fast PTNs -- may be explained by differences in Hodgkin-Huxley potassium kinetics between the two kinds of cell. The same model which faithfully reproduces repetitive firing behavior also reproduces (given appropriate synaptic inputs) the following intracellular events recording during epileptic seizures: (a) a burst of action potentials superimposed on and followed by a PDS, and (b) rapid repetitive firing succeeded by an IPSP. Thus, a single set of parameters can reporduce both normal physiological behavior and 'epileptic' behavior: the particular behavior seen depending on how the cell is stimulated. This overall result is the same as for our model of the CA1 hippocampal cell. It suggests that certain acutely acting epileptogenic agents, e.g. penicillin, may act by increasing synaptic input (perhaps both excitatory and inhibitory) to pyramidal cells, rather than by altering their membrane properties. As in our CA1 hippocampal cell model, bursting seems to be a phenomenon generated by the apical dendrite.
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PMID:Neocortical pyramidal cells: a model with dendritic calcium conductance reproduces repetitive firing and epileptic behavior. 22 13

1. gamma-Aminobutyric acid (GABA)-mediated, Cl(-)-dependent inhibitory postsynaptic potentials (IPSPs) and GABA currents in immature rat hippocampal CA1 neurones were studied using the whole-cell recording technique in brain slices. 2. IPSPs evoked by electrical stimulation were observed in postnatal 2- to 5- (PN2-5), 8- to 13-(PN8-13) and 15- to 20-(PN15-20)day-old CA1 neurones. In the presence of glutamate receptor blockers 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and D-2-amino-5-phosphonovaleric acid (APV), the reversal potential for the IPSP (EIPSP) was near the resting membrane potential (RMP) in the PN2-5 neurones, but 13 and 25 mV more negative than the RMP in PN8-13 and PN15-20 neurones respectively. IPSPs and GABA currents were blocked by the GABAA-receptor antagonists bicuculline or picrotoxin. 3. The reversal potential for somatic GABA currents (EGABA) was examined in the presence of tetrodotoxin (TTX). There was a strong dependence of the EGABA upon the patch pipette [Cl-] ([Cl-]p). indicating that the GABA currents were mediated by a Cl- conductance. In PN2-5 neurones, EGABA agreed with the value predicted by the Goldman-Hodgkin-Katz equation at given concentrations of internal and external anions permeable through GABA-activated Cl- channels, whereas EGABA in older neurones was 8-18 mV more negative. 4. Examination of the relations between EGABA, holding potential, [Cl-]p and resting conductance indicated that the membrane of the PN2-5 neurones was readily permeable to Cl- which followed a passive Donnan equilibrium. Passive distribution of Cl- played a decreasing role in PN8-13 neurones and in PN15-20 neurones. 5. To assess the contribution of outward Cl- co-transport, bath applications of high K+ or furosemide were performed. High K+ and furosemide caused a reversible positive shift of EGABA in PN15-20 neurones. Raising the temperature moved EGABA to a more negative potential, with a Q10 of 5 mV. A similar change of EGABA in response to high K+, but not to furosemide, was found in PN8-13 neurones. 6. The present data indicate the existence of GABAA-mediated inhibitory synaptic connections in CA1 neurones at the earliest stages of postnatal life. During the first postnatal week, Cl- ions are passively distributed and the EIPSP and EGABA are near the RMP.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Development of GABA-mediated, chloride-dependent inhibition in CA1 pyramidal neurones of immature rat hippocampal slices. 182 51

1. Neurones were isolated from the CA1 region of the guinea-pig hippocampus and subjected to the whole-cell mode of voltage clamping, to determine the kinetics of voltage-gated Ca2+ channel activation. 2. Isolated neurones had an abbreviated morphology, having lost most of the distal dendritic tree during the isolation procedure. The electrical compactness of the cells facilitates voltage clamp analysis. 3. Block of sodium and potassium currents revealed a persistent current activated on depolarization above -40 mV, which inactivated slowly when the intracellular medium contained EGTA. The current was blocked by Co2+ and Cd2+, augmented by increases in Ca2+ and could be carried by Ba2+, suggesting that the current is borne by Ca2+. 4. Steady-state activation of the Ca2+ current was found to be well described by the Boltzman equation raised to the second power. 5. The open channel's current-voltage (I-V) relationship rectified in the inward direction and was consistent with the constant-field equation. 6. The kinetics of Ca2+ current onset followed m2 kinetics throughout the range of its activation. Tail current kinetics were in accord with this model. A detailed Hodgkin-Huxley model was derived, defining the activation of this current. 7. The kinetics of the currents observed in this regionally and morphologically defined class of neurones were consistent with the existence of a single kinetic class of channels.
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PMID:Calcium current activation kinetics in isolated pyramidal neurones of the Ca1 region of the mature guinea-pig hippocampus. 245 32

Currents were generated by depolarizing pulses in voltage-clamped, dissociated neurons from the CA1 region of adult guinea pig hippocampus in solutions containing 1 microm tetrodotoxin. When the extracellular potassium concentration was 100 mM, the currents reversed at -8.1 +/- 1.6 mV (n = 5), close to the calculated potassium equilibrium potential of -7 mV. The currents were depressed by 30 mM tetraethylammonium in the extracellular solution but were unaffected by 4-aminopyridine at concentrations of 0.5 or 1 mM. It was concluded that the currents were depolarization-activated potassium currents. Instantaneous current-voltage curves were nonlinear but could be fitted by a Goldman-Hodgkin-Katz equation with PNa/PK = 0.04. Conductance-voltage curves could be described by a Boltzmann-type equation: the average maximum conductance was 65.2 +/- 15.7 nS (n = 9) and the potential at which gK was half-maximal was -4.8 +/- 3.9 mV (mean +/- 1 SEM, n = 10). The relationship between the null potential and the extracellular potassium concentration was nonlinear and could be fitted by a Goldman-Hodgkin-Katz equation with PNa/PK = 0.04. The rising phase of potassium currents and the decay of tail currents could be fitted with exponentials with single time constants that varied with membrane potential. Potassium currents inactivated to a steady level with a time constant of approximately 450 ms that did not vary with potential. The currents were depressed by substituting cobalt or cadmium for extracellular calcium but similar effects were not obtained by substituting magnesium for calcium.
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PMID:Potassium current activated by depolarization of dissociated neurons from adult guinea pig hippocampus. 284 59

1. The Ca2+ permeability of non-NMDA and NMDA receptor channels was studied using a fluorometric flux measurement approach in somata and dendrites of CA1 pyramidal neurones in rat hippocampal slices. For this purpose, the Ca2+ fraction of the total cation current (named 'fractional Ca2+ current') was measured directly from the change in the Ca(2+)-sensitive fura-2 fluorescence at 380 nm excitation wavelength. 2. The fractional Ca2+ current through the somatic NMDA receptor channels was 10.69 +/- 2.13% (mean +/- S.D.) and that through dendritic receptor channels was 10.70 +/- 1.96%. The fractional Ca2+ current was not dependent on the extracellular Mg2+ concentration and its voltage dependence was in agreement with the Goldman-Hodgkin-Katz current equation. 3. AMPA (alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate) or kainate applications produced small but significant Ca2+ entry. Fractional Ca2+ currents of 0.58 +/- 0.34% were measured for somatic AMPA applications, 0.68 +/- 0.20% for somatic kainate applications, 0.66 +/- 0.25% for dendritic AMPA applications and 0.61 +/- 0.16% for dendritic kainate applications. 4. The expression pattern of glutamate receptor subunits encoding messenger ribonucleic acids (mRNAs) was analysed with the single-cell reverse transcriptase-polymerase chain reaction (RT-PCR) approach applied to CA1 pyramidal neurones. The AMPA receptor subunits GluR-A, GluR-B and GluR-C, and the NMDA receptor subunits NR2A and NR2B were found to be abundantly expressed in all CA1 pyramidal neurones tested. 5. This study establishes the fractional Ca2+ current through somatic and dendritic NMDA and non-NMDA receptor channels in CA1 pyramidal neurones. The dendritic, presumably synaptic, NMDA receptor channels are highly Ca2+ permeable and have a fractional Ca2+ current closely resembling that of somatic extrasynaptic NMDA receptor channels. Both somatic and dendritic non-NMDA receptor channels are of the 'low Ca2+ permeable' type and have a fractional Ca2+ current that is about twenty times smaller than that of NMDA receptor channels.
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PMID:Fractional Ca2+ currents through somatic and dendritic glutamate receptor channels of rat hippocampal CA1 pyramidal neurones. 881 9

Human BCL6, also called LAZ3, is a protein involved in gene regulation and abnormal expression of BCL6 and has been implicated in the tumorigenesis of non-Hodgkin lymphoma. We have analyzed the expression of murin bcl6 in pre- and postnatal mouse using in situ hybridization histochemistry and Northern blotting. The developing olfactory epithelium in the nasal cavity was the only tissue displaying a positive bcl6 mRNA signal in the day 14 embryo. At gestational day 17, expression was primarily seen in skeletal muscle, olfactory epithelium, and thymus, and also in the epithelium lining the upper airways and esophagus. In selected tissues from postnatal mouse, bcl6 expression was detected in brain, renal cortex, spleen, and thymus. The expression in brain was restricted to the pyramidal cell layer of the cerebral cortex and the hippocampus regions CA1 and CA2, and the dentate gyrus. Our results show that bcl6 expression is not confined only to organs of the lymphatic system, such as spleen and thymus. Thus, bcl6 may be active as a regulator of gene transcription in many different cell types, including epithelial and nerve cells.
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PMID:Expression of the BCL6 gene in the pre- and postnatal mouse. 964 31

A system of equations governing the activity of hippocampal neuron populations is proposed. This continual firing-rate model is aimed to simulate evoked potentials and synchronous wave activity of the neural tissue. The populations of excitatory and inhibitory neurons and the types of synaptic receptors are distinguished. The model is based on the idea of control and averaging of Hodgkin-Huxley equations, a simple model of a threshold elicitation of population action potential bursts, approximations of synaptic currents by the second-order differential equations, and hyperbolic partial derivative equation of axonal excitation propagation. The model was fitted to intracellular cordings of postsynaptic potentials and postsynaptic currents in CA1 of rat hippocampal slices.
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PMID:[A model for evoked activity of hippocampal neuronal population]. 1250 May 73

Recent studies have shown that place cells in the hippocampal CA1 region fire in a sequence sensitive manner. In this study we tested if hippocampal CA3 and CA1 regions can give rise to the sequence sensitivity. We used a two-layer CA3-CA1 hippocampal model that consisted of Hodgkin-Huxley style neuron models. Sequential input signals that mimicked signals projected from the entorhinal cortex gradually modified the synaptic conductances between CA3 pyramidal cells through spike-timing-dependent plasticity (STDP) and produced propagations of neuronal activity in the radial direction from stimulated pyramidal cells. This sequence dependent spatio-temporal activity was picked up by specific CA1 pyramidal cells through modification of Schaffer collateral synapses with STDP. After learning, these CA1 pyramidal cells responded with the highest probability to the learned sequence, while responding with a lower probability to different sequences. These results demonstrate that sequence sensitivity of CA1 place cells would emerge through computation in the CA3 and CA1 regions.
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PMID:Emergence of sequence sensitivity in a hippocampal CA3-CA1 model. 1760 3

During wakefulness, pyramidal neurons in the intact brain are bombarded by synaptic input that causes tonic depolarization, increased membrane conductance (i.e., shunting), and noisy fluctuations in membrane potential; by comparison, pyramidal neurons in acute slices typically experience little background input. Such differences in operating conditions can compromise extrapolation of in vitro data to explain neuronal operation in vivo. For instance, pyramidal neurons have been identified as integrators (i.e., class 1 neurons according to Hodgkin's classification of intrinsic excitability) based on in vitro experiments but that classification is inconsistent with the ability of hippocampal pyramidal neurons to oscillate/resonate at theta frequency since intrinsic oscillatory behavior is limited to class 2 neurons. Using long depolarizing stimuli and dynamic clamp to reproduce in vivo-like conditions in slice experiments, we show that CA1 hippocampal pyramidal cells switch from integrators to resonators, i.e., from class 1 to class 2 excitability. The switch is explained by increased outward current contributed by the M-type potassium current I(M), which shifts the balance of inward and outward currents active at perithreshold potentials and thereby converts the spike-initiating mechanism as predicted by dynamical analysis of our computational model. Perithreshold activation of I(M) is enhanced by the depolarizing shift in spike threshold caused by shunting and/or sodium channel inactivation secondary to tonic depolarization. Our conclusions were validated by multiple comparisons between simulation and experimental data. Thus even so-called "intrinsic" properties may differ qualitatively between in vitro and in vivo conditions.
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PMID:Pyramidal neurons switch from integrators in vitro to resonators under in vivo-like conditions. 1882 48

Here we report patients with Hodgkin's disease and multiple myeloma, who relapsed/progressed after high dose therapy and autologous stem cell transplantation. In patients who developed aplastic anemia type syndrome, spontaneous tumor regression was observed and concomitantly high titers of serum autoantibodies were found. In order to identify the antibody specificity, two-dimensional electrophoresis, blotting and immunoreactions were used to analyze the peripheral blood stem cell extract with autoantibodies containing serum. The unique protein spot visualized exclusively by serum of patients with aplastic anemia type syndrome was identified as carbonic anhydrase I (CA I, accession No. P00915 and Q7M316) by means of mass spectrometry. The specificity of autoantibodies was confirmed by reaction with commercial CAs I, II, IX and XII. Immunoreaction in Western blots with these CA isoforms differed in sera obtained from patients with various types of the disease. Sera of Hodgkin's disease patients reacted with CA I, II and XII; sera of multiple myeloma patients reacted with the CA I, II, XII and IX. Patients developing and/or possessing CA autoantibodies had a significant survival benefit over those who did not develop CA anhydrase autoantibodies. Possible relevance of the presence of CA autoantibodies and clinical outcome is discussed.
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PMID:Presence of serum carbonic anhydrase autoantibodies in patients relapsed after autologous stem cell transplantation indicates an improved prognosis. 1899 76


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